The occurrence of dramatic changes in mood, behavior, cognition and somatic functioning in some women in relation to the menstrual cycle has recently been the focus of a great deal of public scrutiny. Yet despite fifty years of study, relatively little is known about the relationship between menstruation and disorders of mood. This project addresses itself to the major methodological difficulties characterizing earlier studies and is designed to study the psychobiology and treatment response of women with well defined menstrually-related mood disorders. The longitudinal screening methods employed in the first phase of our study appear capable of distinguishing women with menstrually-related mood syndromes from those who only believe that they have such a syndrome. We are currently measuring potential biological correlates of menstrually-related mood changes by assaying serial blood samples for relevant hormones and by performing neuroendocrine and electrophysiological tests during the symptom-free and symptomatic phases of the menstrual cycle. We are additionally performing double-blind controlled studies of several putative therapeutic agents including progesterone and pyridoxine. The goals of this project are to detect and accurately describe menstrually-related mood disorders, explore their pathophysiology and response to pharmacological and environmental manipulation, and to document the relationship between reproductive endocrine change and disorders of mood as a way of further investigating the neurobiology of psychiatric illness.